The present series of studies have examined the functional activity of rat and human large granular lymphocytes (LGL), the population of cells known to mediate natural killer (NK) and antibody-dependent cell mediated cytotoxicity (ADCC). The adoptive transfer of LGL into rats with depressed NK/ADCC activity was shown to restore antitumor activity, as well as inhibit the development of syngeneic bone marrow stem cells. These results provide the first direct evidence for an important role for LGL in antitumor responses and in the control of bone marrow growth and differentiation. These results also suggest that the adoptive transfer of highly enriched LGL populations should be further considered as one potential immunotherapeutic regimen in cancer patients. In addition, protocols involving the depletion of host NK activity in bone marrow transplantation recipients should be further considered. In other experiments we have shown a number of differences in the organ, age and strain distribution between the NK and ADCC effector cell (K cell) populations. Studies with the BRM, OK432, have shown this agent to augment NK activity and increase survival of tumor-bearing rats. The mechanism(s) by which these LGL function was examined by isolating the granules from rat LGL leukemia cells. These granules contain a "cytolysin" capable of lysing tumor cells. In addition, LGL granules contain molecules which can activate macrophages, a molecule which inhibits the growth of fungi and a molecule which is chemotactic for both LGL and macrophages. These molecules probably account for much of the functional activity of LGL.